Search

Purpose of review No clinical trial in sporadic inclusion body myositis (IBM) thus far has shown a clear and sustained therapeutic effect. We review previous trial methodology, explore why results have not translated into clinical practice, and suggest improvements for future IBM trials. Recent findings Early trials primarily assessed immunosuppressive medications, with no significant clinical responses observed. Many of these studies had methodological issues, including small participant numbers, nonspecific diagnostic criteria, short treatment and/or assessment periods and insensitive outcome measures. Most recent IBM trials have instead focused on nonimmunosuppressive therapies, but there is mounting evidence supporting a primary autoimmune aetiology, including the discovery of immunosuppression-resistant clones of cytotoxic T cells and anti-CN-1A autoantibodies which could potentially be used to stratify patients into different cohorts. The latest trials have had mixed results. For example, bimagrumab, a myostatin blocker, did not affect the 6-min timed walk distance, whereas sirolimus, a promotor of autophagy, did. Larger studies are planned to evaluate the efficacy of sirolimus and arimoclomol. Summary Thus far, no treatment for IBM has demonstrated a definite therapeutic effect, and effective treatment options in clinical practice are lacking. Trial design and ineffective therapies are likely to have contributed to these failures. Identification of potential therapeutic targets should be followed by future studies using a stratified approach and sensitive and relevant outcome measures.

The idiopathic inflammatory myopathies represent a rare group of diseases characterized by autoimmune inflammation of skeletal muscle and other organs. There has been significant recent progress in understanding pathogenesis, phenotyping disease subtypes and investigating effective therapeutic options. Patients typically present with progressive, proximal weakness and elevated muscle enzymes, and often have additional extramuscular manifestations, including skin, respiratory, articular, gastrointestinal and cardiovascular involvement. These extramuscular manifestations can precede or occur in the absence of clinically detectable muscle involvement. There are a multitude of potential differential diagnoses to consider and a careful initial evaluation supported by structured investigations remains critical for accurate diagnosis and timely commencement of appropriate treatment.

Objective The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients. Methods Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case. Results Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify. Conclusion Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05046-4.

Purpose of review To examine recent developments relating to cardiac involvement in the adult idiopathic inflammatory myopathies (IIM) and those inherited muscle diseases which may present in adulthood and mimic IIM.Recent findings Cardiac involvement is a common feature of IIM and inherited muscle diseases. Frequency according to disease subtype varies, with serotype having particular influence in IIM, and genotype in the inherited muscle diseases. Innovative techniques for examining cardiac function have been investigated further, including speckle-tracking echocardiography and cardiac magnetic resonance tomography. The present work has highlighted a likely underestimate of the burden of cardiac disease to date. The complex relationship between IIM, atherosclerosis, and traditional cardiovascular risk factors has been further elucidated. Consensus recommendations for managing patients with inherited muscle diseases and prominent cardiac involvement have been recently published. In addition to supportive care, disease modifying treatments are increasingly becoming available for inherited muscle diseases which may also improve cardiac outcomes.Summary Cardiac involvement is associated with significant morbidity and mortality. We suggest having a low threshold for considering the possibility of cardiac involvement in all patients with muscle disease.

Background Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. Methods Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016–July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. Results We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives. In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives. Individual autoantibody specificities were > 98.2 and > 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7–189.2, p p Conclusions We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies.

The idiopathic inflammatory myopathies (IIM) are heterogeneous and lead to high morbidity and mortality. Knowledge deficits among healthcare professionals could be detrimental to clinical care. Identifying areas of deficient Knowledge, Attitude and Practice (KAP) of IIM can improve physician education and patient outcomes. To assess the proportion of physicians treating IIM with poor KAP and identify the key areas of deficit. An anonymised and validated e-survey (57 questions) was circulated among physicians treating IIM (purposive sampling). Responses were evaluated using the Likert scale for good (> 70% correct response), poor (> 20% chose > 2 answers) and the rest as intermediate consensus. Descriptive statistics were used. Intergroup comparisons were done using non-parametric tests. Of 80 (9.1% of 883) respondents, 90% were rheumatologists and 37.5% academicians. The knowledge base of treating physicians was good in specific domains such as triggers (80–90%), clinical presentation (MDA5, statin myositis, steroid myopathy, anti-synthetase syndrome) (82–92%), IIM mimics (41–89%), investigations (23–92%) and risk of osteoporosis in IIM (79%). There is also an intermediate knowledge base/consensus for outcome measures (30–56%) and response criteria (30–53%). There was poor knowledge and consensus on trials (27–34%), EULAR/ACR criteria (31%) and exercise-based interventions (17–62%). While 90% agree on the need for muscle biopsy to diagnose polymyositis, only one-third advocated it for juvenile and adult DM. Physicians have a good understanding of the triggers, clinical presentation and mimics of IIM. Poor to intermediate knowledge and consensus exists regarding muscle biopsy, outcome measures, response criteria and exercise-based interventions, which could be addressed through future focussed educational initiatives.

A 63-year-old woman was referred to neurology with bilateral severe progressive pain and stiffness in her thighs. The patient had a 3-year history of injecting intramuscular cyclizine into the anterior thigh to treat nausea associated with a longstanding pan-enteric dysmotility syndrome. MRI of the thighs demonstrated fibrotic appearances. A biopsy of the left vastus lateralis and surrounding fascia identified pathology consistent with a fibrous myopathy. The patient was advised to stop intramuscular injections of cyclizine and undergo physiotherapy but she still remained in considerable pain. Although fibrous myopathy occurring as a consequence of recurrent intramuscular drug injections, particularly heroin, has been previously described, this is the first report of fibrous myopathy associated with the use of intramuscular cyclizine. We highlight this rare association and suggest that the long-term use of intramuscular cyclizine be avoided.

Background Sporadic inclusion body myositis (IBM) is a muscle wasting disorder usually affecting those aged over 50 years, characterised by slowly progressive weakness of the distal upper limbs and proximal lower limbs. Particular weakness of pinch, knee extension and ankle dorsiflexion result in functional decline and disability. Weakness-associated functional decline differences between genders has not previously been investigated. This study aimed to investigate for differences of functional decline in men and women with IBM. Methods A cohort of verified adult IBM patients were followed at a single specialist neuromuscular clinic (Royal Victoria Infirmary, Newcastle-upon-Tyne, UK) between 2004-15, with data collected at each clinic visit. Strength of 11 movements was measured via dynamometry at each clinic visit. Patient-reported function was measured via the Neuromuscular Symptom Score (NSS). Generalised linear modelling, adjusted for disease duration, was carried out to identify associations between strength and function (NSS). Pinch, knee extension and ankle dorsiflexion strength measurements were analysed. Modelling was carried out separately for male and female cohorts. Results Data of 75 participants (47% female) was analysed. A total of 591 measurements were taken. Median age at time of IBM diagnosis was 68.8 years. Median baseline NSS score was 45 (IQR 37, 54) for the male cohort and 40 (IQR 29, 45) for the female cohort. The median disease duration of the study cohort was 2.6 years. Reduced function (NSS) was significantly associated with reduced pinch, knee extension and ankle dorsiflexion strength in the male cohort only (Table 1). No significant associations were observed in the female cohort. Conclusion This is the first study to demonstrate that the progression of weakness, in the characteristic muscle groups affected in IBM, impacts on function differently in men and women. These results illustrate the importance of functional assessment in patients with IBM and the importance of focused physiotherapy upon function-dependent muscle groups. Further, potential gender-based differences of weakness-related function in IBM should be considered when designing clinical trials. Disclosures J. Williams None. A. Oldroyd None. J. Lilleker None. H. Chinoy None. J. Miller None.

PURPOSE OF REVIEW: To describe recent advancements in diagnostic and therapeutic approaches to inclusion body myositis (IBM).RECENT FINDINGS: Our understanding of the implications of anti-cytosolic 5'-nucleotidase 1A autoantibody status in IBM and other diseases is increasing. Muscle imaging using magnetic resonance techniques and ultrasound is increasingly being performed and characteristic patterns of muscle involvement may help with diagnosis. Longitudinal imaging studies are likely to help with monitoring and as an outcome measure in clinical trials. Recent small-scale studies of Arimoclomol and Rapamycin have shown promising results and further investigation of these medications is ongoing. Exercise is likely to form an increasingly important facet of management of patients with IBM, but the optimal type of exercise programme to enrol patients in is not yet determined.SUMMARY: Antibody testing and muscle imaging results may improve our ability to diagnose IBM and the availability of effective disease modifying treatments targeting novel non-inflammatory pathways could soon become a reality. It remains the duty of those involved in the management of patients with IBM to facilitate involvement in clinical trials and other research studies.

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, which causes progressive muscle weakness and in severe cases respiratory failure and death. Although the majority of the SMA cases are autosomal recessive, there is an autosomal dominant variant of SMA that primarily affects the lower extremities, known as 'spinal muscular atrophy - lower extremity, dominant' (SMALED). Mutations in the Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene were the first to be associated with SMALED. Here we report a family with SMALED caused by a pathogenic heterozygous missense c.1809 A>T, p.glu603Asp mutation in DYNC1H1. The main clinical features were congenital hip displacement, talipes, delayed motor development, wasting and weakness in lower limbs with relative sparing of upper extremities and very slow disease progression. SMALED is extremely rare and only a handful of families have been reported. Over the years other phenotypes including Charcot Marie Tooth type 2 and hereditary mental retardation with cortical neural migration defects have also been reported to be caused by DYNC1H1 mutations. This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.

Idiopathic inflammatory myopathies represent a rare group of diseases characterized by a central role of autoimmune processes and the inflammation of skeletal muscle. There has been significant recent progress in understanding disease pathogenesis, phenotyping subtypes of disease and investigating effective therapeutic options. Patients typically present with progressive, proximal weakness and functional impairment, and elevated muscle enzymes. There can also have extramuscular manifestations, including skin, respiratory, articular, gastrointestinal and cardiovascular involvement, which can precede or occur in the absence of clinically detectable muscle involvement. There are therefore a multitude of potential differential diagnoses to consider. A conscientious initial evaluation supported by pragmatically structured investigations remains critical to accurate diagnosis and appropriate management of these complex conditions.

Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle. Patients may present with indolent myopathic features, exercise intolerance or recurrent rhabdomyolysis. Diagnostic delays are common and clinicians need a high index of suspicion to recognise and differentiate metabolic myopathies from other conditions that present in a similar fashion. Standard laboratory tests may be normal or non-specific, particularly between symptomatic episodes. Targeted enzyme activity measurement and next-generation genetic sequencing are increasingly used. There are now specific enzyme replacement therapies available, and other metabolic strategies and gene therapies are undergoing clinical trials. Here, we discuss our approach to the adult patient with suspected metabolic myopathy. We outline key features in the history and examination and discuss some mimics of metabolic myopathies. We highlight some disorders of glycogen and fatty acid utilisation that present in adulthood and outline current recommendations on management.

The inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene on chromosome 3 belongs to a family of genes encoding intracellular calcium channel proteins. Such channels are located primarily within the endoplasmic reticular membrane and release Ca2+, an intracellular messenger, which governs numerous intracellular and extracellular functions. We report a family with infantile-onset cerebellar ataxia with delayed motor development and intellectual disability caused by a heterozygous c.805C>T, p.Arg269Trp missense mutation in ITPR1. Both affected family members had postural tremor, hypotonia and dysarthria, but neither had pyramidal signs. Their neuroimaging revealed cerebellar atrophy. Several neurological conditions have been associated with ITPR1 mutations, such as spinocerebellar ataxia type 15 and Gillespie syndrome, and the phenotype may vary according to the location and type of mutations. Spinocerebellar ataxia type 15 is an autosomal dominant disorder, which causes late onset pure cerebellar ataxia. Gillespie syndrome is characterised by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia and cerebellar atrophy. In this report, we provide a detailed phenotypic description of a family with a missense mutation in ITPR1. This mutation has only been reported once before. We also provide a literature review of the various phenotypes associated with ITPR1 gene.

The idiopathic inflammatory myopathies are a group of conditions characterised by inflammation of muscles (myositis) and other body systems. The diagnosis can be challenging because of the many potential clinical features and extra-muscular manifestations, which may be seemingly unrelated. An accurate diagnosis requires up-to-date understanding of the clinical manifestations, different clinical subtypes and appropriate interpretation of investigations, including newly described serological subtypes.This review will detail the approach to the diagnosis of an idiopathic inflammatory myopathy, based on up-to-date knowledge. The recently updated classification criteria and treatment options will also be described.

Background:Since first described, our understanding of polymyositis (PM) has evolved substantially. Patients previously diagnosed with PM may now be better described as having an alternative diagnosis, including immune-mediated necrotizing myopathy (IMNM), connective tissue disease overlap myositis (CTD-OM), anti-synthetase syndrome (ASS) or inclusion body myositis (IBM).Objectives:To apply the current understanding of IIM subtypes to retrospectively review the diagnosis of patients classified as PM at our centre.Methods:We reviewed a cohort of 255 patients from a UK tertiary myositis clinic, with 37 patients classified as PM according to the EULAR/ACR IIM criteria and expert opinion (1). Consensus decisions made as to whether reclassification as an alternative IIM subtype would be appropriate in each case.Results:Thirty-seven patients with PM diagnosis according to EULAR/ACR IIM criteria and expert opinion were included in the analysis. Twenty-six patients (26/37, 68.4%) were female. The mean age at diagnosis was 57 years (SD 16.25) and mean follow up was 5.2 years (SD 4.8).After consensus discussions, ten patients (27%) retained classification as PM, representing 3.9% (10/255) of the original cohort of 255 patients. The remaining 27 were reclassified as follows: 7 CTD-OM (18.9%), 6 IMNM (16.2%), 6 unspecified myopathy (16.2%), 2 DM (5.4%), 1 IBM (2.7%), and 1 non-inflammatory myopathy (2.7%, myofibrillar myopathy). Four patients (10%) had insufficient data available to allow for a defined diagnosis.Of the 10 patients retaining classification as PM, 7 (70%) were female and mean age at diagnosis was 58.9 years. Clinical characteristics are represented in table 1. Mean CK at diagnosis was 2321 IU/L. Four patients (40%) were ANA positive, 8 patients (80%) were tested for the complete myositis antibody panel and 8 (80%) were specifically tested for the presence of HMGCR antibodies (figure 1). EMG revealed a myopathic pattern in 6/7 patients tested, while MRI demonstrated muscle oedema compatible with myositis in 3/5 of the patients that were tested. A complete muscle biopsy report was available in 8/10 PM-classified patients (80%), diffuse HLA-1 upregulation was present in 5 patients (50%), endomysial inflammatory infiltrates in 5 (50%) and perimysial infiltrates (in conjunction with endomysial infiltrates) in 3 (30%). No other specific features were found.Table 1.Clinical features.PM (n=10)CTD-OM (n=7)IMNM (n=6)All (n=37)Pyrexia0001 (2.7 %)Weight loss2 (20%)2 (28.6%)2 (33.3%)6 (16.2 %)Cutaneous rash01 (14.3%)02 (5.4 %)Mechanic’s hands1 (10%)2 (28.6%)04 (10.8 %)Sclerodactyly01 (14.3%)01 (2.7 %)Periungual erythema01 (14.3%)02 (5.3 %)Raynaud’s05 (71.4%)08 (21.6 %)Arthralgia05 (71.4%)08 (21.6 %)Arthritis02 (28.6%)05 (13.5 %)Muscle weakness10 (100%)7 (100%)6 (100%)36 (97.2%)Myalgia3 (30%)5 (71.4%)3 (50%)20 (54 %)Dysphagia3 (30%)5 (71.4%)1 (16.7%)13 (35.1 %)Interstitial lung disease (ILD)03 (42.9%)04 (10.5 %)Malignancy1 (9.1%)02 (33.3%)3 (8.1%)Conclusion:This study confirms that PM can now be considered a rare IIM subtype. A thorough examination, complete myositis antibody panel including HMGCR testing and careful interpretation of the biopsy results is recommended to accurately classify these patients.References:[1]Parker MJS, Oldroyd A, Roberts ME, Lilleker JB, Betteridge ZE, McHugh NJ, et al. The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort. Rheumatol (United Kingdom). 2019 Mar 1;58(3):468–75Disclosure of Interests:None declared

Idiopathic inflammatory myopathies (IIMs) are heterogeneous conditions, and the optimal way to classify patients and divide them into subgroups remains unclear. Could machine learning techniques be the answer to the problem of defining homogeneous disease phenotypes, enabling stratified treatment approaches and the formulation of future IIM classification criteria?

Mitochondrial complex I deficiency is associated with a diverse range of clinical phenotypes and can arise due to either mitochondrial DNA (mtDNA) or nuclear gene defects. We investigated two adult patients who exhibited non-syndromic neurological features and evidence of isolated mitochondrial complex I deficiency in skeletal muscle biopsies. The first presented with indolent myopathy, progressive since age 17, while the second developed deafness around age 20 and other relapsing-remitting neurological symptoms since. A novel, likely de novo, frameshift variant in MT-ND6 (m.14512_14513del) and a novel maternally-inherited transversion mutation in MT-ND1 were identified, respectively. Skewed tissue segregation of mutant heteroplasmy level was observed; the mutant heteroplasmy levels of both variants were greater than 70% in muscle homogenate, however, in blood the MT-ND6 variant was undetectable while the mutant heteroplasmy level of the MT-ND1 variant was low (12%). Assessment of complex I assembly by Blue-Native PAGE demonstrated a decrease in fully assembled complex I in the muscle of both cases. SDS-PAGE and immunoblotting showed decreased levels of mtDNA-encoded ND1 and several nuclear encoded complex I subunits in both cases, consistent with functional pathogenic consequences of the identified variants. Pathogenicity of the m.14512_14513del was further corroborated by single-fiber segregation studies.

The idiopathic inflammatory myopathies are a group of heterogeneous autoimmune connective tissue diseases. Despite increase in the understanding of these conditions, securing a timely diagnosis and accurate subtype classification remains difficult in some cases. This has important implications for patients, where delayed or inappropriate treatments can have a negative effect on outcomes.Several conditions can mimic myositis, including metabolic myopathies, genetic myopathies and neurological disease. In addition, the heterogeneity within the idiopathic inflammatory myopathy spectrum can also create diagnostic confusion, referred to here as ‘myositis chameleons’. This includes inclusion body myositis, immune-mediated necrotizing myopathy, hypomyopathic variants of anti-synthetase syndrome and overlap disease.We highlight the importance of a thorough diagnostic workup, refer to updated classification criteria and emphasize the importance of myositis autoantibody testing. Where diagnostic doubt exists, the involvement of a specialist centre and a multidisciplinary team is vital.

Therapeutic plasma exchange (TPE) involves the extracorporeal separation of plasma from the cellular components of blood with replacement fluid, such as human albumin or fresh frozen plasma. A number of studies across the world revealed that more than one third of TPE procedures were performed for neurological disorders. Myasthenia gravis (MG), Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) were the most frequently cited indications for TPE, followed by multiple sclerosis (MS). However, treatments of these conditions have evolved over the years and it is likely that this has impacted on clinical practice. Here we present our experience of using TPE to treat neurological disorders. We reviewed the medical records of all 63 patients who received 349 procedures over 70 therapeutic cycles between 2012 and 2015 in a tertiary neurology centre. In total only 2 patients with GBS and MG were treated with TPE. The commonest indication was voltage gated potassium channel (VGKC) complex antibody associated disorders followed by CIDP and MS. There were 11 patients with limbic encephalitis. Nine of them had antibodies against VGKC complex and two had N-methyl-D-aspartate (NMDA) receptor antibodies. Sixty four percent of patients with limbic encephalitis and overall 78% of patients responded to TPE. The complication rate associated with this procedure was 8.6 per 100 therapeutic cycle. There was no treatment related mortality. We observed a change in indications of TPE compared to historical studies. It was less frequently used to treated GBS and MG. It was found to be safe and effective.

The idiopathic inflammatory myopathies (IIM) are a rare and heterogeneous group of acquired autoimmune muscle disorders, often referred to as ‘myositis’. Clinical assessment, together with muscle biopsy findings and autoantibody status are key factors to consider when making a diagnosis of IIM, and in stratification of the ‘IIM spectrum’ into disease subgroups. Treatment stratified according to serotype (and in the future, likely also genotype) is increasingly being used to take account of the heterogeneity within the IIM spectrum. Subgroup classification is also important in terms of monitoring for complications, such as malignancy and interstitial lung disease. Disease monitoring should include the use of standardized tools such as the IMACS disease activity outcome measures. Other tools such as muscle MRI can be useful in identifying areas of active muscle inflammation. Treatment outcomes in IIM remain unsatisfactory. The evidence base to guide treatment decisions is remarkably limited. In addition to muscle inflammation, a number of noninflammatory cell-mediated mechanisms may contribute to weakness and disability, and for which no specific treatments are currently available.

Background:Glucocorticoids (GC) are long established as a first line treatment in patients with idiopathic inflammatory myopathy (IIM), in which high dose, long duration treatment is often required. GC usage is associated with a wide range of adverse effects (AEs). The patient perspective on the risks and benefits of GCs is not well studied and no prior studies assesses this issue in IIM patients (1).Objectives:To describe the perspective of IIM patients on GC treatment.Methods:We deployed an online survey distributed using the Myositis UK page on Healthunlocked.com, an online social network for health, with approximately 450 patients registered. Patients with diagnosed IIM were invited to take part on an anonymised basis. Respondents were asked to grade the severity on a Likert scale (1 to 5) of all AEs experienced in relation to GC. Additionally, respondents were asked to write about their concerns and to rate their overall experience with GC treatment.Results:In total, 122 completed surveys were received. Forty five percent (55/122) of respondents had dermatomyositis, 27% (33/122) polymyositis, 10% (12/122) anti-synthetase syndrome, 18% (22/122) other inflammatory myopathies. Seventy-nine percent (96/122) of respondents were female and the mean age overall was 50 years (SD [standard deviation] 14).The median reported current daily dose of prednisolone was 15 mg and median treatment duration was 5.3 years at the time of survey completion. Females were more likely to stay on GCs for longer than males (5.4vs4.7 years, p=0.046).Table 1.Mean severity and frequency for each adverse effect.All respondents(n=122)Male(n=26)Female(n=96)(n=89)≥60 years(n=33)Moon face3.3 (1.9)2 (2.1)*3.6 (1.7)*3.5 (1.8)2.7 (2)Weight gain3.4 (1.7)3.1 (1.6)3.4 (1.8)3.5 (1.7)3.1 (1.9)Acne1.1 (1.5)1 (1.5)1.2 (1.6)1.3 (1.6)0.7 (1.2)Hair loss2 (1.8)0.8 (1.4)*2.4 (1.8)*2.2 (1.8)**1.5 (1.9)**Facial hair2.1 (1.8)0.7 (1.3)*2.5 (1.8)*2.3 (1.8)1.7 (1.8)Thin skin2.2 (1.9)1.8 (2)2.3 (1.8)2.2 (1.9)2.3 (1.9)Bruising2.2 (1.7)2.1 (1.9)2.2 (1.7)2.2 (1.7)2 (1.9)Stretch marks1.3 (1.9)0.9 (1.5)1.4 (1.8)1.5 (1.9)**0.6 (1.2)**Nausea1.4 (1.7)1.6 (1.8)1.4 (1.6)1.5 (1.6)1.2 (1.7)Heartburn1.9 (1.8)1.8 (1.9)1.9 (1.8)2 (1.8)1.5 (1.8)Hunger2.8 (1.7)2.2 (1.9)*3 (1.6)*3 (1.6)2.4 (2)Mood swings2.7 (1.6)2.1 (1.8)2.7 (1.5)2.8 (1.6)2.6 (1.6)Sleep disturbances3.1 (1.5)2.9 (1.7)3.2 (1.4)3.2 (1.5)3 (1.5)Cataracts0.6 (1.3)1.1 (1.8)0.5 (1.1)0.5 (1.2)1 (1.6)Glaucoma0.4 (1.1)0.6 (1.5)0.3 (0.9)0.4 (1)0.4 (1)Hypertension1.6 (1.7)1.8 (1.7)1.5 (1.7)1.5 (1.7)1.8 (1.8)Diabetes0.8 (1.6)1 (1.6)0.8 (1.6)0.7 (1.5)1 (1.8)Water retention2.2 (1.7)1.7 (1.6)2.3 (1.8)2.3 (1.8)1.9 (1.6)Infections2.2 (1.7)2.2 (1.8)2.2 (1.7)2.2 (1.7)2.1 (1.7)Fractures0.5 (1.1)0.5 (1.2)0.5 (1.1)0.5 (1.6)0.5 (1.1)Mean severity on a Likert scale (0-5), mean (SD);*pFrequency (number of patients reporting adverse effect as present), heatmap:White (0-33%), light grey (33-66%), dark grey (66-100%).The mean number of reported AEs to GC treatment per patient was 12 (SD 5). Female respondents reported a greater number of AEs compared to males (12.6vs10.1, p=0.019). The three most commonly experienced AEs were: sleep disturbance (93%), mood swings (86%) and weight gain (86%). Only 54% of respondents agreed that the information given about the potential risks of GC treatment was adequate. Mean severity and frequency of AEs is represented in table 1.Conclusion:Adverse effects are common, and those rated more severe by patients were physical and behavioural (such as weight gain or sleep disturbance). Female patients reported more severe AEs compared to men.References:[1]Van Der Goes MC, Jacobs JWG, Boers M, Andrews T, Blom-Bakkers MAM, Buttgereit F, et al. Patient and rheumatologist perspectives on glucocorticoids: An exercise to improve the implementation of the European League Against Rheumatism (EULAR) recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis. 2010 Jun;69(6):1015–21.Disclosure of Interests:None declared

ObjectivesWith the tools available currently, confirming the diagnosis of inclusion body myositis (IBM) can be difficult. Many patients are initially misdiagnosed with polymyositis (PM). In this observational study at a UK adult neuromuscular centre, we investigated whether amyloid positron emission tomography could differentiate between IBM and PM.MethodsTen patients with IBM and six with PM underwent clinical review, [18F]florbetapir positron emission tomography and MRI of skeletal musculature. Differences in [18F]florbetapir standardised uptake value ratios in skeletal muscle regions of interest were evaluated. Relationships between [18F]florbetapir standardised uptake value ratios and measures of disease severity (clinical and by MRI of skeletal muscle) were assessed.Results[18F]florbetapir standardised uptake value ratios were significantly higher in those with IBM compared with PM for all assessed regions (total-[18F]florbetapir standardised uptake value ratio 1.45 (1.28 to 2.05) vs 1.01 (0.80 to 1.22), p=0.005). For total-[18F]florbetapir standardised uptake value ratios≥1.28, sensitivity and specificity for IBM was 80% and 100%, respectively.Conclusions[18F]florbetapir amyloid positron emission tomography differentiates IBM from PM. Successful development could facilitate accurate diagnosis, inclusion in clinical trials and help avoid unnecessary exposure to potentially harmful treatments.

Objectives To determine prevalence and co-existence of myositis specific autoantibodies (MSAs) and myositis associated autoantibodies (MAAs) and associated clinical characteristics in a large cohort of idiopathic inflammatory myopathy (IIM) patients. Methods Adult patients with confirmed IIM recruited to the EuroMyositis registry (n = 1637) from four centres were investigated for the presence of MSAs/MAAs by radiolabelled-immunoprecipitation, with confirmation of anti-MDA5 and anti-NXP2 by ELISA. Clinical associations for each autoantibody were calculated for 1483 patients with a single or no known autoantibody by global linear regression modelling. Results MSAs/MAAs were found in 61.5% of patients, with 84.7% of autoantibody positive patients having a sole specificity, and only three cases (0.2%) having more than one MSA. The most frequently detected autoantibody was anti-Jo-1 (18.7%), with a further 21 specificities each found in 0.2–7.9% of patients. Autoantibodies to Mi-2, SAE, TIF1, NXP2, MDA5, PMScl and the non-Jo-1 tRNA-synthetases were strongly associated (p, Highlights • Myositis specific autoantibodies very rarely coexist in the one individual allowing endotypes to be more precisely defined. • The association of anti-TIF1 and cancer-associated myositis is confirmed with a cut-off age of over 58 years. • In a large combined European myositis cohort associations of anti-SRP with carditis and anti-Mi-2 with cancer have emerged. • Myositis associated autoantibodies are strongly associated with having myositis in association with another connective tissue disease.

Background The recently published 2017 European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups reflect a long-appreciated need for more accurate case definition in ongoing research in these complex and heterogenous diseases.1 However a number of issues remain unresolved. There was a high frequency of missing data in both the derivation and validation samples, only one of the now numerous myositis specific autoantibodies is included, and certain well recognised IIM subtypes are not specifically classified despite their well phenotyped and differing natural histories, clinical features and treatment modalities.2 3 Objectives To perform an external validation of the EULAR/ACR classification criteria in an incident IIM cohort and examine how classification criteria-assigned IIM subtype correlates with expert opinion. Methods Adults with newly diagnosed IIM attending Salford Royal NHS Foundation Trust Neuromuscular services were identified. A retrospective review of all putative cases was performed, and cases fulfilling a consensus expert-opinion diagnosis of definite IIM included. A broad range of clinical, serological and histological data were collected and each case assigned a single IIM subtype by expert opinion. The EULAR/ACR classification criteria were applied and sensitivity, specificity, positive and negative predictive value calculated, presented with 95% confidence intervals (CI). Results A total of 922 cases were screened with 255 expert opinion definite IIM identified. The sensitivity to diagnose an IIM was 99.6% (97.2–100) and 80.9% (76.0–85.8) for the classification criteria cut-points of ‘probable’ and ‘definite’ respectively. The sensitivity for ‘definite’ IIM improved to 90.2% (86.5–93.8) when biopsy data for 24/34 initially missed cases were excluded. In 94/255 cases the IIM subtype differed between expert opinion and classification criteria, most strikingly in the group subtyped ‘polymyositis’ using the EULAR/ACR criteria, where there was discrepancy in the majority (87/161). Conclusions The criteria performed with high sensitivity in identifying IIM in an external cohort of IIM patients. However, substantial disagreement exists in subtype assignment, especially resulting in a larger proportion of cases of ‘polymyositis’ with heterogeneous features, important to consider in the application of these criteria to subsequent research. References [1] Lundberg IE, Tjarnlund A, Bottai M, Werth VP, Pilkington C, Visser M De, et al. EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis2017;76:1955–64. [2] Betteridge Z, McHugh N. Myositis-specific autoantibodies: An important tool to support diagnosis of myositis. J Intern Med2016;280:8–23. [3] Longo DL, Dalakas MC. Inflammatory muscle diseases. N Engl J Med2015;372:1734–47. Disclosure of Interest None declared

Neurogenic pulmonary oedema (NPO) is a rare clinical syndrome of pulmonary oedema occurring secondary to an insult of the central nervous system (CNS). The exact aetiology of this disorder is unknown. NPO can be fatal and poor awareness and identification of this entity, particularly in terms of misdiagnosis as primary pulmonary or cardiac disease, can result in suboptimal management and outcomes. We describe the presentation and management of a 68-year-old woman with an acute left lateral medullary stroke complicated by pulmonary oedema. The likely aetiology is discussed, and important learning points are highlighted.

Background The idiopathic inflammatory myopathies (IIM) represent a rare and heterogeneous group of multisystem autoimmune diseases. The rarity of IIM has hampered research efforts, resulting in remarkably limited therapeutic evidence. The EuroMyositis Registry was created to pool resources and expertise across the international IIM research community. Objectives To describe the phenotypic characteristics of different IIM subtypes. Associations with malignancy, interstitial lung disease (ILD), cardiac involvement and dysphagia were assessed. Methods Pooled data from the EuroMyositis Registry (from Belgium, China, Czech Republic, Hungary, Italy, Mexico, Norway, Sweden, Switzerland, UK, Vietnam) were obtained. Associations were assessed using logistic regression and multinomial logistic regression with polymyositis (PM) as the reference group. Results Data regarding 3,196 patients were analysed. The UK was the largest contributor (n=1,307). The most common diagnoses were dermatomyositis (34%), PM (32%) and connective tissue disease (CTD)-overlap myositis (15%). In those with anti-synthetase syndrome (7%), 85% had muscle weakness, 86% ILD and 58% arthritis. Overall, 43% had a myositis specific antibody, most commonly anti-Jo1 autoantibodies (20%). Glucocorticoid usage was noted in 98%. Most commonly used disease modifying agents were methotrexate (71%) and azathioprine (50%). Malignancy occurred in 9% and was associated with a diagnosis of dermatomyositis (Relative Risk Ratio [RRR] 1.68, 95% CI 1.09–2.56, p=0.018). Cardiac involvement occurred in 9%, most commonly in those with CTD-overlap myositis (13%), and was associated with a higher Health Assessment Questionnaire disability index (1 versus 0.75, OR 1.40, 95% CI 1.03–1.91, p=0.031). Dysphagia occurred in 39% and was associated with a diagnosis of CTD-overlap myositis (RRR 2.25, 95% CI 1.61–3.15, p Conclusions This large international cohort demonstrates the heterogeneity of IIM and the burden of associated malignancy, ILD, cardiac and gastrointestinal involvement. The EuroMyositis Registry facilitates international collaborative research outputs, underlining the benefits of harmonised data collection methodology between centres. Acknowledgements This work was supported by researchers at the National Institute for Health Research (NIHR) Biomedical Research Unit. The views expressed are those of the authors and not necessarily those of the UK National Health Service, the NIHR or the UK Department of Health Disclosure of Interest J. Lilleker: None declared, J. Vencovsky: None declared, G. Wang: None declared, L. Wedderburn Grant/research support from: The UK JDM Cohort and Biomarker study is supported by grants from the NIHR and Myositis UK, L. Diederichsen: None declared, J. Schmidt: None declared, P. Jordan: None declared, O. Benveniste: None declared, M. G. Danieli: None declared, K. Dankό: None declared, N. T. P. Thuy: None declared, M. Vazquez-Del Mercado: None declared, O. Molberg: None declared, B. De Paepe: None declared, J. De Bleecker: None declared, B. Maurer Grant/research support from: AbbVie, Protagen, EMDO, Novartis, Roche, Actelion, N. Pipitone Speakers bureau: GRAPPA Workshop, Alfa-Wassermann, N. McHugh: None declared, Z. Betteridge: None declared, P. New: None declared, R. Cooper: None declared, W. Ollier: None declared, J. Lamb Grant/research support from: MedImmune, N. S. Krogh: None declared, I. Lundberg Grant/research support from: Astra-Zeneca, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Idera, H. Chinoy Grant/research support from: MedImmune, Novartis

ObjectivesAutoantibodies directed against cytosolic 5′-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5′-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.Materials and methodsData from various European inclusion body myositis registries were pooled. Anticytosolic 5′-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.ResultsData from 311 patients were available for analysis; 102 (33%) had anticytosolic 5′-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.InterpretationDifferences were observed in clinical and histopathological features between anticytosolic 5′-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5′-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.

BackgroundMyotonic Dystrophy type 1 is an inherited multisystem disorder with a European prevalence of 3–15 per 100,000. Cardiorespiratory complications (e.g. arrythmia, respiratory failure) account for around 70% of early deaths. In many cases this could be prevented though periodic screening and timely intervention, including with pacemakers or non-invasive ventilation, where indicated.Recently, international consensus-based care recommendations have been published with a view to reduce mortality by improving quality and standardising care for patients with Myotonic Dystophy type 1. We hypothesised that nationally, adherence to these recommendations is likely to be poor.MethodsWe audited the care of patients with Myotonic Dystrophy type 1 at the Manchester Centre for Clinical Neuroscience (MCCN) and the University Hospital South Manchester (UHSM) Ventilation Clinic against consensus-based care recommendations. A data collection proforma was created based on the recent care recommendations. Retrospective case note review was performed.Results and conclusionData collection and analysis is ongoing. Full results will be presented at the conference along with a quality improvement action plan. These results will also feed in to a planned redevelopment of tertiary neuromuscular services in the region.

Guillain-Barre syndrome (GBS) comprises a group of acute onset immune mediated polyradiculoneuropathies that are the leading cause of acute onset paralysis in the developed world.1 Management incorporates supportive care of the paralysed patient and immunomodulatory treatment. Active prevention and early treatment of complications, including venous thromboembolism (VTE), may help to improve outcomes. Over 25 000 people die in the UK each year as a result of VTE complicating a hospital admission.2 As a result, national guidelines have been produced to support decision-making regarding the most appropriate strategy of VTE prophylaxis, taking into account the bleeding risk associated with the use of anticoagulation.2 Prolonged flaccid limb weakness and the use of intravenous immunoglobulin are risk factors for the development of VTE in patients with GBS.3 While consensus statements regarding VTE prophylaxis in those with GBS do exist, these are often based on evidence from studies involving postoperative patients and as such do not specifically address the risk-benefit profile of various VTE prophylaxis regimens in GBS.4 At a recent mortality review meeting at our institution, we discussed the case of a 45-year-old patient with GBS in the intensive treatment unit (ITU) who died as a result of bleeding from his tracheostomy. Given his acute severe flaccid paralysis, he was prescribed ‘high dose’ (175 units/kg of subcutaneous tinzaparin per day equivalent) low molecular weight heparin (LMWH) for VTE prophylaxis, as per local practice. Concern was raised that this anticoagulant regimen may have contributed to the occurrence of bleeding and that other patients may be similarly at risk. We, therefore, performed an audit to assess the use of VTE prophylaxis in this patient group. Consecutive patients admitted with GBS (excluding those with Miller Fisher syndrome and Miller Fisher-GBS overlap) to our institution between …

Purpose In a significant number of patients developing epilepsy in adult life, the aetiology of their seizures remains unclear. Antibodies directed against the voltage gated potassium channel complex (VGKC Ab) have been identified in various cohorts of patients with epilepsy, although the role of these antibodies in epilepsy pathogenesis is not fully known. Method We reviewed the notes of 144 patients with unexplained adult onset epilepsy who had been tested for VGKC Abs. We collected data on their clinical syndrome, investigation results and response to treatment. Results We identified 6 (4.2%) patients who had titres of >400pM. One of the six patients was positive for LGI1 and another for CASPR2 subunit antibodies. All patients were given immunotherapy and experienced improvement in seizure control. No patient had the clinical syndrome of limbic encephalitis. Conclusion Patients with otherwise unexplained epilepsy and positive VGKC Abs are a heterogeneous group. In our cohort there was an overall favourable response to immunotherapy but further prospective studies are needed to determine the significance of these antibodies and the optimum treatment regimen for patients.

Background The idiopathic inflammatory myopathies (IIM, myositis) are a heterogeneous group of chronic autoimmune disorders causing considerable physical and mental health impact. There is a lack of formalised guidance defining best practice for the management of myositis, contributing to inconsistent care provision and some patients feeling isolated and unsupported. To address these issues, we evaluated the clinical services available to adults with myositis in the UK. We then created patient-centred standards of care using a structured process involving patients, their relatives and caregivers, physicians and allied healthcare professionals. Methods After an initial focus group, the clinical services available to patients with myositis were evaluated using a patient-completed questionnaire. Draft standards of care were created, each addressing deficits in care provision identified by patients. In response to feedback, including a two-stage modified Delphi exercise, these draft standards were iteratively improved until consensus was reached. Accompanying plain language versions of the standards of care and an audit tool were also created. Results We identified issues regarding diagnostic pathways, access to specialist services, advice and support regarding employment, medication-related adverse events and the treatment of extra-muscular manifestations. Fifteen standards of care were drafted. After modification, agreement was reached on eleven final standards of care. Conclusion These patient-centred standards of care for adults with myositis provide a benchmark for the evaluation of local practice. Their implementation will promote consistent good practice across care providers and empower patients when seeking access to local services. Electronic supplementary material The online version of this article (10.1186/s41927-017-0002-7) contains supplementary material, which is available to authorized users.

We thank Cavagna et al 1 for their thoughtful analysis relating to our recent publication.2 Several important points are raised, many of which we also referred to. It is of great interest and reassurance that the demographics and clinical features of antisynthetase syndrome (ASS) are broadly similar between the AENEAS (American and European NEtwork of Anti-Synthetase syndrome) and EuroMyositis cohorts. Clearly the frequency of interstitial lung disease and arthritis differs due to the sources of case ascertainment. This highlights …

Cerebral amyloid angiopathy affects the small-to-medium-sized cerebral arteries most commonly resulting in asymptomatic microhaemorrhages and symptomatic lobar brain haemorrhages. More unusually, it may present as an acute or subacute leukoencephalopathy. Its mechanism is unknown but probably relates to altered permeability of cerebral blood vessels that results from endothelial dysfunction secondary to β-amyloid accumulation in the vessel wall.1 ,2 There is sometimes associated vessel wall inflammation, termed ‘cerebral amyloid-related inflammation’.3 We describe a challenging case with a relapsing encephalopathic syndrome and discuss its implications. A 72-year-old man presented to the emergency department having awoken that morning with confusion, disorientation and visual hallucinations. Thirty minutes later, he had a generalised tonic–clonic seizure followed by postictal agitation, during which he was non-cooperative and non-attentive. On examination, there were no lateralising neurological signs although he was in a state of delirium, with a Montreal Cognitive Assessment score of 9/30. His blood pressure was 215/115 mm Hg. CT scan of head is shown in figure 1. We made a working diagnosis of acute ischaemic stroke with symptomatic seizure and commenced aspirin and sodium valproate. His blood pressure fluctuated during his admission (systolic between 141 and 201 mm Hg and diastolic 79 and 145 mm Hg). His clinical status improved steadily over the subsequent 4 days and he was able to go home. Figure 1 Axial CT brain scan demonstrating an area of hypodensity …

Voltage-gated potassium channel (VGKC) complex antibodies have been associated with a spectrum of presentations including peripheral nerve hyperexcitability (PNH), Morvan’s syndrome, autoimmune encephalopathy, epilepsy and recently psychosis.We retrospectively reviewed the medical records of 70 patients from the Greater Manchester Neuroscience Centre, who had tested positive for VGKC-complex antibodies between 2012 and 2015 to identify the clinical relevance of positive results.The majority were diagnosed with autoimmune encephalopathy(19) followed by epilepsy(14), psychosis(10) and PNH(6). The remaining fifteen had other neurological presentations and six had no primary neurological disorder. 39/70 patients who had antibody titres>400 pM, were diagnosed with autoimmune encephalopathy(19), epilepsy(9), psychosis(4), PNH(3) and other disorders(4). 24/39 patients, who received treatment with one or a combination of corticosteroids, intravenous immunoglobulins, cyclophosphamide, plasma exchange, azathioprine or rituximab, had a diagnosis of autoimmune encephalopathy(18), epilepsy(2), psychosis(2) and malignancy(2). 16/24 were treatment responsive. 3/31 patients with lower titres were also treated, but only one with the classic phenotype (PNH) responded to treatment.The classic phenotype often had a titre >400 pM. PNH may have a titre ≤400 pM. The patients without classic presentations typically had titres≤400 pM. Consistent with previous studies, clinical phenotyping and antibody titre helped to determine the relevance of VGKC-complex antibodies.

Therapeutic plasma exchange (TPE) is often used to treat confirmed or suspected immune-mediated neurological disorders. Our experience with TPE at a tertiary neurosciences centre is reported. In this retrospective study, we reviewed the medical records of all 63 patients receiving TPE at the Greater Manchester Neuroscience Centre between 2012–2015. During one procedure, 1–1.5 plasma volumes were removed and replaced with isotonic 4.5% human albumin solution. A typical therapeutic cycle was consisted with 5 procedures within 14 days. A total of 349 procedures were performed during 70 therapeutic cycles. Anti-VGKC antibodies-mediated disorders (n=11), chronic inflammatory demyelinating polyneuropathy (10) and multiple sclerosis (9) were the three commonest indications for TPE. It was used as the first-line treatment in 6% of patients, whilst in 75% it was the second-line therapy. Majority of patients (89%) following TPE required further immunosuppression. 75% of patients had a favourable clinical outcome with TPE. The adverse event rate was 8.6 per hundred treatment cycles (bleeding=1, central line infection=2, venous thromboembolism=3). TPE is being used commonly for the treatment of immune-mediated neurological disorders and is associated with a low adverse event rate. Overall, we observed favourable clinical outcomes following TPE.

Introduction The inpatient resources required to meet the needs of patients with Functional Neurological Disorders (FNDs) are uncertain, although significant contributions from neurologists, physiotherapists, psychologists and others are required. Accurate quantification of this is necessary to support care arrangement planning. We examined the inpatient activity linked to the care of patients with FNDs on a tertiary acute neurology ward to evaluate this issue. Methods A retrospective case-note review of patients discharged from the Acute Neurology Unit at the Greater Manchester Neuroscience Centre over four months was performed. Data collected included demographics, diagnosis and length of stay. Results Overall 127 patients were identified. 16% had a diagnosis of FND. Of these, 60% had non-epileptic attack disorder (NEAD), 30% paralysis, 5% blindness and 5% a movement disorder. Patients with FNDs were significantly younger (mean 35 years versus 52 years, p Discussion Patients with FNDs, particularly NEAD, represented a significant proportion of inpatient activity. This information will support planning our FNDs service to ensure it meets the needs of this patient group.

Background Antibodies against the voltage-gated potassium channel (VGKC) complex are typically associated with neuromyotonia, Morvan’s syndrome, limbic encephalitis and epilepsy. The exact role and efficacy of therapeutic plasma exchange (TPE) in such disorders is unclear. We report our experience of using TPE in this setting. Methods We retrospectively reviewed the medical records of 11 patients with anti-VGKC antibodies associated disorders receiving TPE at the Greater Manchester Neuroscience Centre from 2012–2015. Results The median age was 62 years. Their clinical features include seizure, confusion, cognitive decline, rigidity, muscle cramp, myokymia, altered sensation and hallucination. Brain MRI was abnormal in five patients. CSF analysis showed raised protein in five and lymphocytic pleocytosis in one. The median anti-VGKC antibody titre was 3310 pM. In addition, IVIg was used in three patients. All received corticosteroids and subsequent choice of steroid-sparing agent was rituximab, azathioprine, mycophenolate or methotrexate. A sustained favourable response to TPE was observed in eight cases. There was no response in three and only one had transient response. Conclusion This retrospective study suggests that TPE for neurological disorders associated with anti-VGKC antibodies have high rates of favourable response, which is consistent with previous studies. Prospective controlled studies are required to confirm this.